title: Long-term treatment with intravenous bisphosphonates in metastatic breast cancer: a retrospective study.
abstract: Bisphosphonates are important therapies used to reduce the risk of skeletal-related events in patients with bone metastases from breast cancer (BC). This retrospective cohort study evaluated the incidence of osteonecrosis of the jaw (ONJ) and renal impairment in women (n = 221) with bone metastases from BC treated with intravenous bisphosphonates from January 1999 to June 2008. In the long-term cohort, 159 patients received pamidronate (n = 9), zoledronic acid (n = 110), or both (n = 40) for ≥24 months. The comparator group consisted of patients treated with intravenous bisphosphonates for 12-23 months (n = 62). After 39 months' median follow-up, six of 159 patients developed ONJ (3.8%; median 38.5 treatment cycles and 44 months' exposure) in the long-term cohort. Of patients who developed ONJ, 50% resumed intravenous bisphosphonates after a 12-month treatment holiday. Renal impairment developed in 19 patients in the long-term cohort (11.9%; median 26 treatment cycles and 26 months' exposure). Of these 19 patients, 11 (57.9%) recovered baseline renal function and seven (36.7%) showed partial recovery. After modification of the intravenous bisphosphonate regimen, 17 of 19 patients (89.4%) resumed therapy. Of the 62 patients in the comparator cohort, one patient developed ONJ (1.6%) and six developed renal impairment (9.7%). Similar incidence rates of ONJ and renal impairment were observed for the long-term and comparator cohorts. Times to ONJ or renal impairment also were similar across intravenous bisphosphonate type. Long-term (≥24 months) intravenous bisphosphonate use in metastatic BC is well tolerated, with low incidences of ONJ and renal impairment.
authors.affiliation: Hematology/Oncology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
authors.forename: Adam M
authors.initials: AM
authors.lastname: Brufsky
authors.forename: Susan M
authors.initials: SM
authors.lastname: Sereika
authors.forename: Aju
authors.initials: A
authors.lastname: Mathew
authors.forename: Onishi
authors.initials: O
authors.lastname: Tomifumi
authors.forename: Vikramjit
authors.initials: V
authors.lastname: Singh
authors.forename: Margaret
authors.initials: M
authors.lastname: Rosenzweig
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D059266:Bisphosphonate-Associated Osteonecrosis of the Jaw / Q000453:epidemiology*; D001859:Bone Neoplasms / Q000556:secondary*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015331:Cohort Studies; D004164:Diphosphonates / Q000009:adverse effects*; D005260:Female; D006801:Humans; D015994:Incidence; D007275:Injections, Intravenous; D007674:Kidney Diseases / Q000139:chemically induced*; D008875:Middle Aged; D012189:Retrospective Studies
chemical_list: D004164:Diphosphonates
keywords: adverse events; bisphosphonate; breast cancer; pamidronate; zoledronic acid